Culture supernatants from four species of skin microorganisms (P. acnes, P. avidum, P. granulosum and S. epidermidis) were assayed for smooth muscle contracting substances which are indicative of inflammatory activity. At least three types of smooth muscle contracting substances were detected. These were: first, a substance active on a rat fundic strip preparation and antagonized by N,N-DMT. Activity was enhanced when cultures were grown in the presence of tryptophan. This substance was probably tryptamine. Second, a substance active on a guinea-pig ileum preparation and antagonized by mepyramine. Activity was enhanced when cultures were grown in the presence of histidine. This substance was probably histamine. Third, a substance active on a rat fundic strip preparation but not antagonized by N,N-DMT, mepyramine, atropine or indomethacin. Activity was enhanced when cultures were grown in the presence of glucose. This activity was probably due to acetate, propionate or other short-chain fatty-acid salts. Chromatographic analysis confirmed the presence of histamine, tryptamine and short-chain fatty acids in the culture supernatants. These substances if produced in vivo may cause or contribute to inflammation and pain directly without the prior mediation of the immune system. Cell extracts of Propionibacterium species were analysed by bioassay for the presence of prostaglandin-like compounds. These could not be detected in any of the eight strains of organisms tested.