The common protozoon, Giardia intestinalis, parasitizes the upper small intestine of man, and is often refractory to treatment by metronidazole. Defective oxygen-scavenging mechanisms have been implicated as a cause of metronidazole resistance of another flagellate Trichomonas vaginalis, where metronidazole is also the most common drug treatment. Oxygen consumption of six clinical isolates of G. intestinalis and one line selected for resistance to metronidazole was measured over 0-50 microM-O2 using an oxygen electrode open for gas exchange. At > 30 microM-O2, inhibition of respiration was demonstrated in all seven stocks. Apparent oxygen affinities (KmO2) were found to range from 0.5 to 5.2 microM-O2; however, isolates from patients who failed to respond to treatment with metronidazole did not have measurably defective O2-scavenging capabilities compared with metronidazole-sensitive isolates. These strains did, however, show elevated NADPH-oxidase activities compared with metronidazole-sensitive strains. Results indicate that biochemical mechanisms of drug resistance in G. intestinalis may be quite different from those operating in T. vaginalis.