The effect of cortisol on the cellular concentration of translatable procollagen mRNAs was studied in cultured human skin fibroblasts. Cortisol selectively decreased the amount of procollagen mRNAs, in comparison to the total mRNA activity, when the cells were grown in enriched medium conditions, i.e., with 10% newborn calf serum. The selective decrease was first observed after 6 h exposure to 1 microM cortisol. In depleted medium conditions, i.e., with 2% newborn calf serum, the initial response was a stimulatory one, followed after about 12 h by a decrease in the procollagen mRNA activity. The results suggest that the selective inhibitory effect of cortisol on the cellular concentration of translatable procollagen mRNA species needs an optimal serum concentration. Furthermore, the results give support to the hypothesis that the decrease in the procollagen mRNA concentration after cortisol administration is a secondary response, preceded by the induction of some intracellular regulation system.