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Thus California and its Spanish Colonization would be different from earlier efforts to simultaneously introduce missionaries and colonists in their world conquest schemes. Organized by the driven Franciscan administrator Junipero Serra and military authorities under Gaspar de Portola, they journeyed to San Diego in 1769 to establish the first of 21 coastal missions.

Despite the romantic portraits of California missions they were essentially slave labor camps, intended primarily to benefit the colonizers. The overall plan was to militarily intimidate the local Indians with armed conquistors, who always accompanied the Franciscans in their missionary efforts and then teach them to be Gods Children, again under the watch full eyes of the conquisitors. Any time a Indian or groups of Indians tried to disobeyed their masters, they were tortured and killed.

Scientific study of demographic trends during this period indicate the Indians of the America's did not possess any natural immunities to introduced European diseases. Maladies such as smallpox, syphilis, diphtheria and even children' ailments such as chickenpox and measles caused untold suffering and death among Indians near the Spanish centers of population. Even before the outbreak of epidemics, a general population decline was recorded that can be attributed to the unhygienic environment of colonial population centers.

A series of murderous epidemic diseases swept over the terrified mission Indian populations. Beginning in 1777 a voracious epidemic likely associated with a water born bacterial infection devastated Santa Clara Valley Costanoan children. Again children were the primary victims of a second epidemic of pneumonia and diphtheria expended from Monterey to Los Angeles was recorded in 1802. By far the worst of these terrifying epidemics began in 1806 and killed thousands of Indian children and adults. The Disease that killed so many thousands has since been identified as the measles. 

Sadly, the missionary practice of forcibly separating Indian children from their parents and incarcerating children from the age of six in filthy and disease ridden gender barracks most likely increased the suffering and death of above mentioned epidemics. Excessive manual labor demands of the missionaries and poor nutrition probably contributed to the Indians inability to resist such infections.

Faith in their traditional shaman suffered when native efforts were ineffective in stemming the tide of suffering and death at the hands of the Missionaries. With monotonous regularity, missionaries and other colonial officials reported upon the massive death and poor health of their Indian laborers. Researchers have determined that perhaps as much as 60% of the population decline of mission Indians was due to introduced diseases.

The missions were authorized by the crown to "convert" the Indians in a ten year period. Thereafter they were suppose to surrender their control over the missions livestock, fields, orchards and building to the Indians. But the padres never achieved this goal and the lands and wealth were eventually stolen from the Indians.