Twelve female rats weighing approximately 150 g received in the submaxillary gland a pellet capable of releasing 3.5 microg GHRH/h for 60 days. Another eight sex- and weight-matched animals received placebo pellets in the same place. After two months the animals were killed, heart blood was collected and pituitary and submaxillary glands were carefully dissected. Pituitary GH content in both placebo- and GHRH-treated animals showed similar values, but plasma GH and IGF-I levels were significantly lower in the animals carrying GHRH pellets (P<0.03); these animals also had a significantly higher GH content in the submaxillary gland (19.2+/-8 ng/mg protein) compared with the placebo-treated group (1.1+/-0.3 ng/mg protein). GH mRNA was present only in the submaxillary gland of GHRH-treated rats as determined by PCR-Southern blot and by in situ hybridization methods. It is concluded that high local GHRH levels are capable of inducing transdifferentiation in submaxillary gland cells to synthesize GH.