In this prospective study, the relationship between biochemical markers of bone turnover and changes in bone mass of the lumbar spine and proximal femur were evaluated. Thirty-two postmenopausal women were randomly assigned to either conjugated equine estrogen (0.625 mg) and medroxyprogesterone acetate (5.0 mg. synthetic E/P, n = 15) or micronized 17-β estradiol (1.0 mg) and micronized progesterone (200 mg. micronized E/P, n = 17) administered daily and continuously for 13 cycles. Demographic and baseline hormonal profiles did not differ (p > 0.05) between the groups. Osteocalcin. bone-specific alkaline phosphatase. type 1 procollagen peptide. and crosslinked N-terminal telopeptide of type 1 collagen were measured in both serum and urine, and bone mineral density was assessed prior to and after the 13-cycle treatment period. Lumbar (L2-L4) bone density improved (p < 0.01) by 5.0% and 3.8% in both the synthetic E/P and micronized E/P groups, respectively. Proximal femur bone density improved by 2.6% (p < 0.05) and 3.1% (p < 0.01) in the synthetic and micronized E/P groups, respectively. Overall. markers of bone turnover decreased 18–47% in both treatment groups (p < 0.01). Specifically, markers of formation decreased: serum osteocalcin by 46.8% and 19.5%. bone-specific alkaline phosphatase by 42.9% and 18.9%. and type 1 procollagen peptide by 25.8% and 29.0% in the synthetic E/P and micronized E/P groups, respectively. Rates of bone resorption, as determined by crosslinked N-terminal telopeptide of type I collagen levels, were reduced by 46.4% and 43.4% in the synthetic E/P and micronized E/P groups, respectively. Among the markers, baseline values for type I collagen peptide were correlated with changes in bone mineral density at the lumbar spine (r = 0.399. p < 0.026) and proximal femur (r = 0.387. p < 0.05). The percent change from baseline levels of type 1 collagen peptide was correlated (r = 0.381. p < 0.035) with change in bone mineral density at the proximal femur only. These data suggest that postmenopausal women with high bone turnover rates, as indicated by increased type I procollagen peptide levels, may be more sensitive to HRT as demonstrated by increased bone mineral density of the lumbar spine and proximal femur. Moreover, hormonal preparation does not appear to have differential effects on markers of bone metabolism and bone mass.