The production of a prolactin (PRL)-like substance by mitogen-stimulated immunocompetent cells has been reported previously for a number of species. The Snell dwarf mouse has a deficiency in thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) as a result of a defect in the pituitary Pit-1 promoter. Since the gene for PRL is present in the dwarf mouse pituitary but not activated it was of interest to determine whether a similar deficiency existed for splenocytes from the dwarf animal. Irradiated splenocytes from dwarfs and normal littermates were cocultured in synthetic AIM-V medium with Nb2 cells and stimulated with concanavalvin A (Con-A). The 3H thymidine incorporation into Nb2 cells in cocultures was quantitated by the addition of mouse PRL to Nb2 cells alone. Splenocytes from dwarf mice produced significantly less PRL-like activity (p < 0.02) than did splenocytes from normal animals. The administration of thyroxine (T4) to dwarf mice increased body weight (BW) gain and the number of splenocytes/g BW. The administration of recombinant bovine GH but not recombinant bPRL further increased body weight gain over T4 alone but neither pituitary hormone had any additional effect on the number of splenocytes/g BW over that noted for T4 alone. Prolactin and GH alone had no effect on splenocyte numbers/g BW. The decreased production of PRL-like activity in the dwarf mouse was not altered by either GH or PRL injection. The injection of T4 alone and in combination with pituitary hormones increased the production of PRL-like activity by dwarf splenocytes to values similar to that observed for normal animals.