Phospholipase A2 (PLA2), total and pancreatic, were quantitated in 91 sera of patients with systemic sclerosis (SSc). The mean total PLA2 of 216 +/- 161 U/ml (SD) was significantly lower (p less than 0.001) than in controls (317 +/- 128 U/ml). In 55 of 91 patients (60%) PLA2 was more than 1 SD and in 6 (7%) more than 2 SD below the normal mean. Serum pancreatic PLA2 was also significantly lower in SSc. The prevalence of low serum total PLA2 was significantly greater (p less than 0.001) than in healthy adults, or in patients with rheumatoid arthritis, systemic lupus erythematosus or vasculitis. Repeat assays of PLA2 activity in 10 patients with SSc documented persistence of low PLA2. Among 76 patients with SSc with complete clinical and laboratory assessment, there were 48 with low and 28 with normal (or slightly elevated) PLA2. These 2 groups showed no differences in disease manifestation or therapy. The group with low serum PLA2 had lower erythrocyte sedimentation rates (p less than 0.0005) and lower neutrophil (p less than 0.05) and monocyte counts (p less than 0.025) in the peripheral blood. The finding of low serum PLA2 activity adds to the spectrum of arachidonic acid pathway abnormalities associated with SSc, and may in part be related to the paucity of inflammatory changes observed in this disease.