Recently, murine peritoneal exudate polymorphonuclear leucocytes (PMNs) have been proved to secrete complement C3. In this report we show the secretion of C3 by normal human blood PMNs. ELISA assay was used to detect secreted C3 in culture supernatants of PMNs, while immunoperoxidase staining was used for intracellular C3 detection. 12-o-tetradecanoyl phorbol 13 acetate (TPA) had a flushing effect on C3 secretion by PMNs but not macrophages, suggesting a special C3 storing capability in PMNs. Dioctanoyl glycerol, mezerein and calcium ionophore A23187 caused the same marked increase in C3 secretion by PMNs. This suggests the contribution of protein kinase C and the calmodulin pathway in the mechanism of C3 secretion, similar to murine peritoneal exudate PMNs. In some cases of systemic lupus erythematosus, C3 secretion by blood PMNs was increased but no similar response to TPA could be detected.