Serum human parathyroid hormone (1±34)[hPTH(1±34)] levels and the anabolic effect of hPTH(1±34) were compared after administration using multiple pulses of iontophoresis or subcutaneous (sc) intermittent injections to ovariectomized (OVX) Sprague Dawley rats. Triple-pulse iontophoretic administration of hPTH(1±34) (doses: 40±400 mg/patch), achieved by repeated 30-min applications of a 0.1 mA/cm 2 current separated by 45-min rest intervals, produced three sharp peaks in the serum hPTH(1±34) level in response to application of the current. Each peak appeared at the end of the 30-min current application period and was proportional to the hPTH(1±34) dose. Compared with once-daily sc injections (7 pulses/week), triple-pulses iontophoretic administered 3 times/week (9 pulses/week) for 4 weeks produced dose-related increases in the bone mineral density (BMD) of the distal 1/3 femur. For the sc administration, the relative BMD values using the vehicle injection as a reference standard for 1, 5, and 25 mg/kg/day were 104, 114, and 121%, respectively. For iontophoretic administration, the relative BMD values using the placebo patch as a reference standard for 40, 120, and 400 mg/patch were 104, 110, and 116%, respectively. The increase in the BMD plotted against the area under the hPTH(1±34) serum level±time curve (AUC) over 1 week resulted in similar straight lines in the 9 pulses/week iontophoretic administration and the 7 pulses/week sc administration groups. The estimated iontophoretic dose giving an equivalent BMD to once-daily sc administration at 5 mg/kg/day was 120 mg/patch. These ®ndings strongly suggest that three iontophoretic pulses administered on alternate 350