Variation in fibronectin (Fn) levels and white blood cell counts (WBC) following staphylococcal enterotoxin B (SEB) or SEB + cryoprecipitate containing Fn challenge was studied in New Zealand white rabbits. Increased plasma Fn levels were observed 2 h after the intravenous injection of SEB and peaked at 48–72 h (from a mean level 194.6 ± 4.5 µg/ml prechallenge Fn level to a 72-hour postchallenge mean level of 407.9 ± 25.4 µg/ml). Fn levels then decreased over the succeeding 5 days to approximately prechallenge levels. The total WBC count decreased by 88% within 2 h after the SEB injection. A slow increase in circulatory WBC was observed over the next 24 h. SEB caused an increase in plasma Fn levels and decreased WBC counts with lymphopenia that was followed by a normal lymphocyte count within 5 days. These data suggest that an acute-phase reaction was induced by interleukin-1. Fn prophylaxis provided no change in clinical signs when given at the time of SEB injection.