The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta in the cerebrospinal fluid (CSF) of 66 patients with coccidioidal meningitis during therapy with fluconazole were measured by ELISA. The median concentration of TNF-alpha was 15.2 pg/mL for 322 samples; for IL-1 beta, it was 4.7 pg/mL for 316 samples. There were no significant changes in the level of either cytokine over 24 months of follow-up nor was there an association between the initial CSF concentrations of TNF-alpha and IL-1 beta and subsequent fluconazole treatment failure. Over time, concentrations of IL-1 beta were significantly associated with both clinical symptoms and white blood cell counts in CSF. These results indicate that CSF levels of TNF-alpha and IL-1 beta are relatively low compared with those associated with acute bacterial meningitis.