OBJECTIVE: This study was designed to prospectively examine differential effects of sustained "high" and "low" serum prolactin levels on bone mineral density and peripheral markers of bone metabolism. METHOD: A dual-energy X-ray absorptiometer was used to measure bone mineral density. Peripheral markers of bone formation and resorption were used to measure bone metabolism in 14 Caucasian female patients with schizophrenia treated with risperidone or olanzapine monotherapy over 12 months. RESULTS: Analyses of variance failed to show an association between elevated prolactin and bone mineral loss over time. However, higher rates of bone formation and resorption were seen in those with high prolactin levels. CONCLUSIONS: The results failed to show that elevated prolactin accelerates bone mineral density loss. However, sustained hyperprolactinemia did have an impact on the rate of bone metabolism. Perhaps higher prolactin levels over longer time periods are necessary before the metabolic processes become uncoupled, leading to bone mineral density loss.