To evaluate the differential effects of portacaval shunting (PCS) on the morphological changes that occur in humans with portal-systemic encephalopathy, male rats underwent either PCS (13) or sham operations (10). Normal adult rats (6) were used as controls. All animals were killed 5 to 7 weeks after the surgery. The wet weight of the testes was obtained. Hematoxylin-eosin (HE)-stained sections at 5-micrometers thickness were used for stereological analysis using an image analysis system. Apoptosis was assessed quantitatively in HE and in in situ end-labeling (ISEL)-stained slides, while mitotic activity and mast cell numbers were assessed in 20 high-power fields. There was a significant reduction in the testicular mass (664 mg) in PCS rats in comparison with sham (2,199 mg) and control (1,937 mg) rats (P <.00001). The thickness of germinal epithelium was significantly reduced in PCS rats (64 micrometers) compared with sham (126 micrometers) and control groups (108 micrometers). The number of tubules per square millimeter and the mean curvature were significantly increased in PCS rats (P <.00001). There was a 112-fold increase in apoptosis in PCS rats (112) in comparison with the control and sham-operation groups (1.2 and 0.7, respectively). Mitosis was significantly reduced in the PCS group (P =.0089), but mast cells were unchanged. The results suggest that PCS in the absence of liver dysfunction produces testicular atrophy by reduction in mitosis, maturation arrest, and increased apoptosis of the germinal epithelium. PCS may therefore be responsible for gonadal atrophy that occurs with advanced liver disease in humans.