OBJECTIVE: Assessment of the effectiveness and safety of high daily 125 microg (5,000 IU) or 250 microg (10,000IU) doses of vitamin D(2) during 3 months, in rapidly obtaining adequate 25 hydroxyvitamin D (25OHD) levels. DESIGN: Longitudinal study. SUBJECTS: Postmenopausal osteopenic/osteoporotic women (n = 38) were studied during winter and spring. Median age (25-75th percentile) was 61.5 (57.00-66.25) years, and mean bone mineral density (BMD) was 0.902 (0.800-1.042)g/cm(2). Subjects were randomly divided into three groups: control group (n=13): no vitamin D(2), 125 mug/day (n=13) and 250 microg/day (n=12) of vitamin D(2) groups, all receiving 500 mg calcium/day. Serum calcium, phosphate, bone alkaline phosphatase (BAP), C-telopeptide (CTX), 25OHD, mid-molecule parathyroid hormone (mmPTH), daily urinary calcium and creatinine excretion were determined at baseline and monthly. RESULTS: For all subjects (n=38), the median baseline 25 hydroxyvitamin D (25OHD) level was 36.25 (27.5-48.12) nmol/l. After 3 months, 8% of the patients in the control group, 50% in the 125 microg/day group and 75% in the 250 microg/day group had 25OHD values above 85 nmol/l (34 ng/ml). Considering both vitamin D(2) groups together, mmPTH and BAP levels diminished significantly after 3 months (P<0.02), unlike those of CTX. Serum calcium remained within normal range during the follow-up. CONCLUSIONS: The oral dose of vitamin D(2) required to rapidly achieve adequate levels of 25OHD is seemingly much higher than the usual recommended vitamin D(3) dose (20 mug/day). During 3 months, 250 microg/day of vitamin D(2) most effectively raised 25OHD levels to 85 nmol/l in 75% of the postmenopausal osteopenic/osteoporotic women treated.