The effects of GH and PTH on cancellous histomorphometry were determined in the proximal tibial metaphysis of hypophysectomized (HYPOX) sexually mature female rats. HYPOX resulted in uterine atrophy and a loss in body weight. Longitudinal bone growth ceased and bone formation was greatly reduced. There were decreases in cancellous bone area, trabecular number, and trabecular thickness. Intermittent treatment with GH did not influence uterine weight in HYPOX rats. However, GH resulted in resumption of whole body weight gain, as well as maintenance of normal longitudinal bone growth. Additionally, GH partially maintained bone formation in HY POX rats and did not have a significant effect on steady state messenger RNA levels for osteocalcin. Intermittent treatment with PTH had no effect on whole body weight gain, uterine weight, or longitudinal bone growth. In contrast, PTH increased bone formation compared with the baseline, HYPOX, and GH-treated HYPOX rats, and dramatically increased osteocalcin messenger RNA levels compared with the latter two groups. The increased bone formation was primarily due to an increase in osteoblast number; the mineral apposition rate, an index of osteoblast activity, was increased compared with control and GH-treated rats but not compared with baseline values. Interestingly, neither treatment influenced indices of bone resorption.