A total of 21 calves were inoculated i.v. with 1 of the following isolates of bovine viral diarrhea virus (BVDV); CD87 (n = 10), NY-1 (n = 3), NADL (n = 5), or were sham-inoculated with virus-free medium (n = 3). Subsequent to inoculation, platelet counts were monitored to detect differences between noncytopathic (CD87, NY-1) and cytopathic (NADL) isolates in their ability to induce thrombocytopenia. Platelet count decrease throughout infection was statistically analyzed by comparing the slope of the line drawn from the count on the day of infection to the lowest count achieved by that calf. Significant difference was observed in the CD87-inoculated calves and in the NY-1-inoculated calves, compared with those of the same control group. Significant difference was not observed in the slope of platelet count decrease between the cytopathic NADL-infected calves and control-group calves. The data indicate that noncytopathic BVDV isolates may more easily induce thrombocytopenia than do cytopathic isolates in immune-naive, immunocompetent calves; acute infection with 1 cytopathic BVDV isolate (NADL) did not induce thrombocytopenia. In addition, although each calf seroconverted, virus was rarely isolated from mononuclear cells obtained from calves with cytopathic infections. At some point after infection, virus was always isolated from each of the calves undergoing noncytopathic infections, and occasionally, transient association of noncytopathic BVDV antigen with platelets was observed during these infections.