Growth hormone(GH)-producing pituitary adenomas are morphologically heterogeneous and frequently contain not only GH immunoreactivity but also variable numbers of prolactin (PRL) immunopositive cells. Paraffin sections of 59 surgically removed GH- and/or PRL-producing adenomas classified by histology, immunocytochemistry (ICC) and electron microscopy were studied using in situ hybridization (ISH) for GH and PRL mRNA and combined with ICC for the coded hormones. Somatotroph adenomas (10 densely and 10 sparsely granulated tumours) and mammosomatotroph adenomas (10 cases) contained both GH mRNA and GH immunoreactivity. In 4 densely and 4 sparsely granulated somatotroph adenomas and 4 mammosomatotroph adenomas, only GH mRNA and its product were found. In 28 cases (6 densely and 6 sparsely granulated somatotroph adenomas, 10 mixed somatotroph-lactotroph adenomas and 6 mammosomatotroph adenomas) both GH and PRL mRNA were present, although no PRL immunoreactivity was not in 2 densely granulated somatotroph adenomas. In these cases, ISH for PRL mRNA combined with GH immunostaining revealed the presence of variable numbers of mammosomatotrophs. In 9 acidophil stem cell adenomas only PRL mRNA and its product were found; one tumour expressed both GH and PRL mRNA and their products. Nine lactotroph adenomas contained only PRL mRNA and PRL immunoreactivity. The results show that GH and/or PRL mRNA content could not be correlated with ICC for coded proteins and ultrastructural features. The mammosomatotrophs were more numerous using ISH when compared with ICC. Somatotroph, mammosomatotroph and mixed adenomas are closely related and they can be considered to represent one basic tumour type originating in a cell committed to GH production. This may undergo clonal differentiation towards a mammosomatotroph and further to the lactotroph line. The results also indicate that lactotroph adenomas arise in a cell committed to PRL production. Acidophil stem cell adenomas seem to be more closely related to lactotroph cells than somatotroph.