We describe a new, simple procedure for obtaining and studying mononuclear phagocytes from inflammatory synovial fluid. The viability and functional characteristics of these macrophages have been carefully checked. This technique has been used to evaluate the macrophagic synthesis of prostaglandins in 16 patients with evolutive rheumatoid arthritis. Significant amounts of prostaglandins, mainly PGE2 and TxB2, are released and increased after zymosan administration. The three tested prostaglandins (PGE2, PGF2 alpha and TxB2) responded in a similar manner. The in vitro PG biosynthesis and the number of harvested adherent cells are negatively correlated with the synovial fluid volume but positively correlated with the disease activity. In fact, we found an heterogeneity among the analyzed macrophages; these can be divided into two populations with marked differences in their PG biosynthesis. The one with the highest synthesis corresponded to the more severe disease.