We investigated a patient (W.B.) with chronic symptomatic giardiasis despite seven separate courses of either quinacrine or metronidazole who was cured by combined quinacrine and metronidazole. After isolating Giardia lamblia from W.B., we cultured the trophozoites to make the following observations. In vitro drug testing showed that (a) W.B.'s organisms were not more drug resistant than three other isolates and that (b) W.B.'s organisms were more sensitive to combined quinacrine and metronidazole than to either drug alone. Isolates of Giardia lamblia from W.B. and 3 other patients did not produce detectable enterotoxin in four different assays. W.B. had normal levels of circulating iminunoglobulins, detectable intestinal immunoglobulin A, circulating immunoglobulin G anti-Giardia lamblia antibodies, and lymphocyte responsiveness to solubilized Giardia lamblia. However, monocytes-macrophages from W.B. exhibited reduced killing for Giardia lamblia compared with normal subjects. Conclusions: (a) The chronicity of our patient's infection was not due to the organism having unique properties of drug resistance. (b) Combined quinacrine and metronidazole, which cured our patient's chronic giardiasis, should be tried in patients in whom infection persists after single drug therapy. (c) The diarrhea in our patient was probably caused by a mechanism other than Giardia lamblia-induced secretion by currently recognized enterotoxins. (d) Reduced cellular cytotoxicity for Giardia lamblia may have contributed to the persistence of our patient's infection and should be suspected in other patients with chronic giardiasis. © 1982, American Gastroenterological Association. All rights reserved.