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The neophytes at San Francisco de Asis were drawn from the Miwok and Patwin native people. While there were no large scale conflicts or revolts at this mission there were many many runaways. Mission life was difficult at this mission because of the weather and climate and the padres finally opened up a hospital mission at San Rafael in 1817.
The highest recorded population at this mission was 1,807, in 1821. By 1832 (the last year for which records are available) the population had declined to 204 due to a high death rate, so many runaways amd the opening of San Rafael.