The influence of tobacco smoke has been investigated on the growth rate and histology of prostate cancer, both in untreated tumors and in those subjected to fractionated irradiation. METHODS. Twenty-five rats were implanted bilaterally with Dunning R3327 tumor fragments at 10 weeks of age. Approximately 3 months later, they were randomly allocated to two groups, one of which was exposed to tobacco smoke for an hour each day, 5 days a week. Three weeks later the groups were further subdivided into two groups which acted as controls or were subjected to 5 daily doses of 6 Gy. The tumors were measured weekly to construct growth curves. At a fixed time, 9 weeks or 20 weeks later, the animals were sacrificed and the tumors were removed for histological evaluation of the tissue composition. Sections from each tumor were scored in a morphometric analysis of the fraction of the area of tumor that was occupied by (epithelial) tumor cells, by stroma, or by luminal spaces. In addition, the density of mast cells was assessed in adjacent sections stained with toluidine blue. RESULTS. Smoking caused only minor changes in the growth rates of both the control and the irradiated tumors. At the cellular level, smoking caused a small but significant increase in the fraction of tumor cells relative to controls. Irradiation also caused a small but significant decrease in tumor cell fraction compared to controls, even after 20 weeks of regrowth. This difference was reduced in the smoking and irradiation group. The main difference observed was in the mast cell numbers. Smoking caused a 4-fold increase in mast-cell density. Irradiation caused an even greater increase (25-fold). The combination of smoking and irradiation resulted in an intermediate increase (10-fold). CONCLUSIONS. Long-term smoke exposure can slightly alter the growth rate and morphology of Dunning R3327 rat prostatic adenocarcinoma, but our study does not show a negative effect on the outcome of radiation treatment of this tumor model. We have also demonstrated a highly elevated number of mast cells in the irradiated group, and have shown that smoke exposure significantly depressed the radiation-induced enhancement of the number of mast cells.