Direct effects of histamine on collagenous and non-collagenous protein synthesis by human skin fibroblasts were studied. Fibroblasts derived from human skin were incubated with various concentrations of histamine. Collagen and non-collagenous protein synthesis were measured by incorporation of 3H-proline. Both collagen synthesis measured as protein-bound hydroxyproline and non-collagenous protein synthesis measured as protein-bound proline increased in the presence of histamine at concentrations of 10(1)-10(2) micrograms/ml. Total RNA was extracted and m-RNA levels of various proteins were estimated by dot blot analysis, and densitometrically quantified. The levels of alpha 1(I) collagen and beta-actin m-RNA were clearly increased at the same concentrations. m-RNA levels of alpha 1(III) collagen were also increased but the rate was lower than that of alpha 1(I) collagen. No alteration of beta-tubulin m-RNA level was observed at the same concentrations. These results demonstrate that stimulation of collagen synthesis by histamine is pretranslationally controlled.