Local and systemic tolerance and drug pharmacokinetics were evaluated after a single intravenous infusion of 75 to 1,000 mg of trospectomycin or placebo in 96 healthy volunteers. No clinically significant changes, trends, or abnormalities were observed in the vital signs, electrocardiograms, or laboratory test results; however, there were some statistically significant dose effects or dose-by-time interactions on some of the measures. Mild, transient, local reactions at the infusion site were reported by 20% of the trospectomycin-treated and 22% of the placebo-treated subjects. No irritation of the surrounding tissue was noted when extravasation occurred. Mild, transient, perioral-facial numbness, which was probably drug-related, was the most commonly reported systemic adverse drug experience, occurring in 17 of 64 trospectomycin-treated subjects, but only at doses of 600 mg and above. Pharmacokinetic analyses showed that after a 1,000-mg intravenous dose of trospectomycin, the mean serum half-life was 2.18 hr, the mean area under the curve (AUC) was 157.0 hr x micrograms/ml, the mean maximum concentration (Cmax) was 82.4 micrograms/ml, the mean time to maximum concentration was 25.0 min, and the elimination rate (Ke) was 0.33 hr-1. The Ke and half-life did not vary with dose, and both Cmax and AUC showed a strong linear trend. From 48% to 62% of the dose was excreted in the urine during the first 48 hours after infusion. Under the conditions of this study, intravenous trospectomycin was well tolerated by human subjects at single doses up to and including 1,000 mg.