• The effect of a single prophylactic dose of tin protoporphyrin on the carbon monoxide (CO) excretion rate of antibiotic-treated neonatal rats before and after hematoma formation was evaluated. The CO excretion rate, reflecting the rate of bilirubin production, of tin protoporphyrin-treated (TP-H) rats 24 hours after injection of 65 mole of tin protoporphyrin per kilogram (time [t] = 0 hours) was approximately 18% lower than those of the saline-control (S-C) and saline-hematoma (S-H) rats, but this difference was no longer evident at t=43 hours. After hematoma formation at t=44 hours, the CO excretion rate of the S-H rats increased rapidly; this increase was delayed and lessened in the TP-H rats. At eight hours posthematoma (t = 52 hours), the CO excretion rate of the TP-H rats was significantly lower than that of the S-H rats, 53±2 vs 73±3 μL/kg/hr, respectively. A maximal rate of 89±5 μL/kg/hr was reached 25 hours posthematoma in the S-H rats (t= 69 hours), as compared with 80±3 μL/kg/hr at 44 hours posthematoma in the TP-H rats (t= 88 hours). The recovery of injected blood as CO over a 68-hour study period was approximately 90% for the S-H rats and approximately 65% for the TP-H rats. At t=112 hours, hepatic heme oxygenase activity of the TP-H rats was still significantly lower than that of the S-H and S-C rats; however, plasma bilirubin concentrations of all three groups were similar. These studies demonstrate that tin protoporphyrin is an effective in vivo inhibitor of endogenous heme catabolism as measured by the CO excretion rate in antibiotic-treated neonatal rats with and without artificially created hematomas.