Large MtTW15 tumors, which secrete growth hormone (GH) and prolactin (PRL), are composed of ovoid, elongated, and angular cells which demonstrated interdigitating processes and junctional complexes. The majority of the cells were essentially agranular, but two types of granulated cells were identifiable. One class of granulated cells contained moderate to sparse populations of round dense-cored granules measuring up to 250 nm in diameter. Rod-shaped to filamentous mitochondria with an electron-dense matrix were characteristic of a second class of granulated cells with pleomorphic granules of various sizes and electron densities. Images of exocytotic release of the round dense-cored granules were frequently seen, but were not observed with the pleomorphic granules, many of which were judged to be lysosomes. Superimposition immunocytochemistry revealed hormones only in the granulated cells with round to ovoid granules. Morphometry indicated that hormone specific subpopulations of tumor cells can be identified since PRL secretory granules were significantly smaller than GH secretory granules (149 ± 6 nm for PRL versus 221 ± 9 nm for GH, P < 0.001). The vast majority of immunopositive cells contained only GH or PRL, but a few were observed containing both hormones. Ovoid to irregular-shaped nuclei, large lipid inclusions, numerous free ribosomes and polyribosomes, moderate development of the rough endoplasmic reticulum, and prominent Golgi profiles were characteristics of all cell types. Irrespective of the presence or absence of cytoplasmic granular elements, particles resembling viruses were encountered in many tumor cells, and these frequently appeared to be budding into the cisternae of the endoplasmic reticulum.