Anterior pituitary gland of the spontaneous dwarf rat (SDR) with isolated growth hormone (GH) deficiency was studied using immunocytochemistry, cell count and in situ hybridization. The standard immunocytochemistry of five anterior pituitary hormones [adrenocorticotropic hormone (ACTH), luteinizing hormone, thyroid-stimulating hormone, prolactin (PRL) and GH] and S-100 protein failed to detect any cytological difference between normal rats and SDRs, except for the size of different types of cells which were smaller in SDR than in normal rats, and GH cells which were undetectable in the SDR. The cell count study again showed lack of immunoreactive GH cells in the SDR. The population of PRL cells was significantly reduced in the SDR by 40% in male and 30% in female when compared to those of the control. The population of ACTH cells was larger in the male SDR. The population of the immunonegative cells was calculated by subtracting the sum of the percentages of immunopositive cells from 100, and it was found to be remarkably increased in the SDR. The population of immunonegative cells was about 55% in both male and female SDRs, whereas it was calculated to be 18.7% (male) or 10.2% (female) in the control rats. In situ hybridization study using GH cRNA indicated the presence of a considerable number of cells which express GH mRNA in the SDR as well as in the control rats. These results taken as a whole suggest the presence of a number of dysfunctional GH cells in the SDR. It is also revealed in this study that reduced PRL cell population may be responsible for the reduction of the PRL secretory function in this animal.