The reproductive and behavioral teratogenic effects of paternal lead (7439921) exposure were studied in rabbits. The study was part of a project of the National Toxicology Program to determine if the rabbit was a suitable animal model for human reproductive toxicity studies. Groups of seven male Dutch-Belted-rabbits were injected subcutaneously (sc) with 0 to 3.85mg/kg lead as lead-acetate (301042) three times weekly for 15 weeks (wk) in a preliminary study. The lead concentrations were designed to produce target blood lead concentrations of below 5 micrograms per deciliter (microg/dl) (control), 50, or 110microg/dl. The rabbits were then mated with untreated female rabbits. Litter sizes were determined at delivery. The offspring were weighed periodically between postnatal days (PNDs) five and 35. Consumption of a 3% sucrose solution by the offspring was monitored. Animals were tested for exploratory activity in a figure of eight maze 30 minutes daily on PNDs 15, 20, 25, and 30. The experiment was repeated using groups of 15 male Dutch-Belted-rabbits that were now injected with lead- acetate to produce target blood lead concentrations of 0, 20, 40, or 80microg/dl (main study). In the preliminary study, 16 male rabbits produced viable litters, there being a mean number of six live births per litter in each treatment group. Significant postnatal offspring mortality occurred. By PND 10, only one litter in the 110microg/dl group had more than one pup per litter (pup/litter). Six litters in the 50microg/dl group had an average of 3.2pup/litter. No significant treatment related effects on offspring body weight gain or sucrose solution consumption were seen. Activity in the figure of eight maze, as measured by the number of entries and activity counts, was significantly decreased on PND25 in offspring in the 110microg/dl group. In the main study, 57 male rabbits delivered viable litters. The mean number of pup/litter in all treatment groups varied from 6.6 to 7.6. Nearly half of the offspring died within 1wk after birth. No treatment related effects on body weight gain were seen. Figure of eight maze activity by offspring in the 40 and 80microg/dl groups was significantly decreased on PND 25. The authors conclude that these data suggest that rabbits can be used to detect postnatal functional deficits following paternal exposure to lead or other xenobiotics. The high rate of postnatal death in rabbits, compared to rats, makes the use of rabbits for routine screening less favorable than rats. The results suggest that exploratory activity of rabbit pups may be affected by paternal exposures that produce blood lead concentrations of 40microg/dl or higher.