A human serum thymic factors (SF) stimulated cyclic adenosine-3' ,5'-monophosphate (cAMP) synthesis in normal mouse thymocytes. Such stimulation was no longer observed when thymocytes were depleted of hydrocortisone (HC)-sensitive cells. It was concluded that SF selectively stimulate cAMP in HC-sensitive cells. Furthermore, incubation of thymocytes with SF enlarged the population of HC-resistant thymocytes. These results suggest that SF might act on HC-sensitive thymocytes increasing their cellular cAMP level and inducing their transformation in HC-resistant cells.