Chemiluminescence produced by normal cells was reduced in response to zymosan which was opsonized with serum from patients on prophylactic lithium therapy, compared to control serum from normal subjects (68 +/- 3.1 vs. 93 +/- 3.4 mV/5 X 10(5) cells). Preincubation of normal cells with serum from patients also resulted in reduced chemiluminescence activity when the cells were stimulated with autologous serum-coated zymosan (47 +/- 4.5 vs. 64 +/- 6.3 mV/5 X 10(5) cells). Spontaneous complement conversion was increased in the serum of patients on lithium therapy (46.3 +/- 3.8 vs. 25.3 +/- 2.5% conversion). These studies demonstrated that lithium, at safe therapeutic levels (0.4-0.9 mmol/liter), significantly altered complement conversion and had a marked affect on chemiluminescence activity by normal cells.