Previous observations have suggested that retinoids might be useful for the treatment of rheumatoid arthritis. In this study we examined the effects of various retinoids on collagenase production by adherent human peripheral blood mononuclear cells in culture. We have previously shown that these cells, consisting predominantly of monocyte-macrophages, actively synthesize and secrete collagenase upon stimulation with concanavalin A. The cells were incubated in serum free medium with all-trans-retinoic acid, 13-cis-retinoic acid, all-trans-retinal, or Ro 10-9359 (trimethylmethoxyphenyl retinoic acid ethyl ester) for up to 72 hours, and the collagenase activity was determined with [3H]proline labelled type I collagen as substrate. The incubation of mononuclear cells with all-trans-retinoic acid in the concentration range 10(-7)-10(-5) mol/l resulted in a dose dependent inhibition of the collagenase production. All-trans-retinal was also a potent inhibitor, whereas 13-cis-retinoic acid and Ro 10-9359 in a concentration of 10(-5) mol/l had a lesser effect. Control experiments indicated that the inhibition of collagenase production by all-trans-retinoic acid did not result from inhibition of total protein synthesis nor could it be explained by induction of an inhibitory molecule. These results indicate that retinoids with distinct structural features can inhibit collagenase production by monocyte-macrophages, and suggest a role for retinoids in the treatment of rheumatoid arthritis.