BACKGROUND: Osteoporosis is a complication of hyperparathyroidism (HPT). Hyperhomocysteinemia (HHCy) is an independent risk factor for osteoporotic fractures. We hypothesize that HHCy correlates with bone disease in HPT. METHODS: A prospectively collected database of 250 patients treated for HPT was reviewed. Patients were categorized into 3 groups: group I, normal renal function; group 2, mild renal insufficiency; and group 3, secondary HPT with end-stage renal disease on dialysis. Serum homocysteine levels, markers of bone metabolism, and bone density studies were examined. RESULTS: The prevalence of HHCy in group 1 (208 patients) was 5%, in group 2 (23 patients), 82%, and in group 3 (19 patients), 78%. Mean (+/-SD) preoperative homocysteinemia (HCy) levels in groups 1, 2, and 3 were 9.3 +/- 4.0, 20 +/- 10.2, and 20.6 +/- 12.3 micromol/L, respectively. Elevated serum markers of bone metabolism increased significantly with decreasing renal function. CONCLUSIONS: Prevalence of HHCy is low in HPT patients with normal renal function. It is significantly greater in those with dialysis-independent and -dependent renal insufficiency. HHCy correlates with other serum markers of bone metabolism in HPT and may be useful for monitoring progression or improvement.