Hypothalamic expression of growth hormone-releasing hormone (GHRH) was quantified morphologically in dwarf mice which exhibit spontaneous genetic GH absence. Mouse GHRH mRNA was assessed by in situ hybridization; densitometric evaluation of total mRNA in dwarfs showed levels 2.3-fold higher than in phenotypically normal siblings (p < 0.01); assessment of mRNA per neuron by autoradiographic grain counting indicated a 2.5-fold increase per cell in dwarfs (p < 0.005). GHRH peptide was evaluated immunocytochemically using a new mouse-specific antiserum; numbers of neurons containing detectable levels were 3-fold higher in dwarfs (p < 0.005). The increase in GHRH mRNA corroborates that reported previously in the GH-deficient little mouse, and after hypophysectomy in rats; GHRH peptide increase contrasts with previous reports of the effect of acute GH removal by hypophysectomy, in which GHRH levels fell. The results suggest that chronic GH deficiency is accompanied by increased translation as well as transcription of GHRH.