Coccidioidomycosis (CM) has been recognized in inmates of California State prisons since 1919, where it has been diagnosed in inmates of various correctional facilities inside and outside the known endemic areas. In recent years construction of new prisons within endemic areas has led to an increase in the number of cases of CM. In 2005 and 2006, the Pleasant Valley State Prison (PVSP) near Coalinga and Avenal State Prison (ASP) near Avenal on the western side of the San Joaquin Valley have been particularly affected. In 2005, our serologic testing yielded 150 new cases from PVSP and 30 from ASP. The incidence rate in 2005 for PVSP (population approximately 5,000) was at least 3,000 per 100,000, and this will be exceeded in 2006. Some cases diagnosed in early 2006 likely were infections that were acquired in 2005. Some cases are medically managed on site, but very ill inmates have had care in nonprison facilities. Precise numbers of patients who were hospitalized were not made available to the author. Estimates of the cost per patient have varied from $8,000 in the 1990s to $30,000 more recently. Thus, this disease has important medical, demographic, and financial implications for the state.