Eighty-five symptomatic patients with parasitologically confirmed, recently acquired giardiasis were treated in a comparative trial of 2.4 g of metronidazole either once or on two successive days or 2.0 g of tinidazole once. The follow-up period was eight weeks; the parasitological follow-up consisted of 871 stool and 30 duodenal specimens. Reinfections were unlikely. The rates of success were: metronidazole, single dose, 13 of 26; metronidazole, two doses, 24 of 31; and tinidazole, single dose, 26 of 28. Clinical and parasitological effects were parallel in nearly all cases. Tinidazole was more effective, produced fewer side effects, and was recommendable as the drug of choice in single-dose therapy. Pharmacokinetic explanations for therapeutic failure was sought with use of a bioassay of drug concentrations in serum. The outcome of therapy was not related to serum levels at 1hr or 24 hr, or to the rate of elimination. The mean serum half-lives of active metronidazole and tinidazole were 9.5 and 13.0 hr, respectively.