The leukotriene C_4 (LCT_4) releasing capacities of calcium ionophore A23187 stimulated human monocytes were studied using specific radioimmunoassay in patients with systemic lupus erythematosus (SLE) and normal controls. In 7 normal controls, monocytes (1×10^6) released larger amounts of LTC_4 (6.9 ± 1.4ng) than polymorphonuclear leukocytes (1.5 ± 0.8ng) (p<0.01). LTC_4 release from monocytes in 30 SLE patients (3.6 ± 1.6ng) was decreased compared with that in 16 normal controls (6.7 ± 1.6ng) (p<0.001). LTC_4 release in 18 patients with active disease and that in 12 patients with inactive disease was similar, being 3.2 ± 1.5ng and 4.1 ± 1.6ng, respectively. LTC_4 release was studied vertically in six patients when they were taking 30 mg/day of prednisolone and when they were taking no prednisolone. There was no difference in LTC_4 release regardless of the prednisolone doses. These findings support the concept that monocytes from SLE patients have intrinsic defects in producing mediators of immuno-regulation.