This study investigates the multihormonal character of pituitary adenomas at the ultrastructural level. The growth hormone (GH)- and prolactin (PRL)-secreting adenomas under study consisted of many moderately or densely granulated cells and a few sparsely or slightly granulated cells. The GH-secreting adenomas showed well-developed cytoplasmic organelles and many large (250 nm or more) or medium-sized (200 nm) secretory granules, as well as a few small (70-150 nm) secretory granules. The PRL-secreting hormones exhibited poorly or slightly developed cyto-plasmic organelles and several small secretory granules. Morphologically and antigenically, these sparsely or slightly granulated cells were similar to those of clinically non-functioning (CN-F) adenomas, which appeared identical to cells expressing little or slight immunoreaction to pituitary hormones at the light microscopic level. As well as those of CN-F adenomas, the small secretory granules of both densely and sparsely granulated cells expressed little or only slight antigenicity of various hormones. Con-comitantly showing slight or moderate antigenicity of hormones biochemically unrelated to GH or PRL, the medium-sized or large secretory granules larger than 140 or 160 nm significantly exhibited intense PRL or GH antigenicity, respectively (Fisher's exact test; P < 0.05 or 0.01). Their GH or PRL antigenicity increased as they grew larger. Showing intermediate cells between sparsely and densely granulated cells, two CN-F adenomas, however, appeared to develop into growth hormone-secreting adenomas. This study led us to conclude that pituitary adenomas may originate from sparsely granulated cells with slight biochemically unrelated hormones, and that their hormonality may be selectively activated singly or multiply in the course of their development.