At a public hospital in Georgetown, Guyana, 44 patients seeking treatment for symptomatic, slide-confirmed malaria were given standard chloroquine (CQ) therapy and followed for 28 days. The patients apparently had pure infections with Plasmodium falciparum (14), P. vivax (13) or P. malariae (one), or mixed infections either of P. falciparum and P. vivax (17) or of P. falciparum, P. malariae and P. vivax (two). Each received supervised treatment with 10 mg CQ base/kg on each of days 0 and 1, and 5 mg/kg on day 2. On the day of enrollment (day 0), the patients complained of fever (100%), headache (100%), malaise (94%), myalgia (79%), nausea (67%), vertigo (49%) and vomiting (33%). Many (39%) were ill enough to confine themselves to bed. On day 4, fewer of the subjects complained of fever (15%), headache (15%), malaise (6%), myalgia (21%), nausea (6%), vertigo (24%) or vomiting (0%) despite the relatively high (>48%) risk of therapeutic failure. The cumulative incidence of parasitological failure against P. falciparum was 15% at day 4, 33% at day 7 and 48% at day 14. All of the P. vivax and P. malariae infections cleared before day 4 and none recurred by day 7. Two infections with P. vivax recurred later (on day 14 or 28) but in the presence of less than adequate, whole-blood concentrations of CQ plus desethyl-chloroquine (i.e. <100 ng/ml). Taken together, the results indicate a high risk of therapeutic failure of CQ against P. falciparum but also indicate that resistance to CQ in P. vivax occurs infrequently in Guyana.