Pamaquine (6-methoxy-8-amino [N-diethylaminoisopentyl] quinoline) is recognized to be a potentially dangerous drug. However, a definitive appraisal of its hazard had not been achieved at a time when the further exploration of the antimalarial activity of the 8-aminoquinolines was considered advisable. Pamaquine toxicity can involve the gastro-intestinal tract, the central nervous system, and the circulating blood. Symptoms referable to the gastro-intestinal tract and the central nervous system may be annoying, but there is no evidence that they constitute a hazard to life or persist beyond the termination of therapy. Effects on the blood do constitute a serious hazard and are considered in this paper. MATERIALS AND METHODSMost of the patients utilized as subjects either were having malaria at the time of the observations or had had the disease from one to six weeks previously. None of the patients had malaria long enough to be considered likely subjects for the development of blackwater fever. Most subjects were suffering from asymptomatic neurosyphilis and many had received prior antiluetic therapy. (e) Fragility of erythrocytes to hypotonic saline. A 2 per cent suspension of erythrocytes in sterile physiological saline was prepared from blood containing one drop of saturated potassium oxalate per 5 ml. of blood. 0.5 ml. of the cell suspension was added as soon as possible to 2 ml. each of 0.9 per cent sodium chloride (control), to distilled water (total hemoglobin), and to a series of sodium chloride dilutions usually ranging from 0.48 per 121

Paludrine, N1-p-chlorphenyl-N5-isopropylbiguanide acetate, was found by British workers to be ;he most active antimalarial of a series of synthetic guanidines and biguanidines (1, 2). It possesses high activity against the erythrocytic asexual parasites of both vivax and falciparum malaria and is practically non-toxic at therapeutic doses (3, 4). Previous study of the compound has included extensive prophylactic, curative and suppressive trials by the Australian Malarial Unit at Cairns in experimental sporozoite and trophozoite induced vivax and falciparum malaria (5) and curative trials in naturally acquired relapsing Southwest Pacific vivax malaria (6). The drug has a prophylactic action in falciparum malaria which is complete in single doses as low as 25 mgm. The prophylactic action in vivax malaria is less definite, although the incubation periods of patients in the Cairns studies were systematically prolonged, and subinoculations from infected patients showed that this was due to an effect upon the initial tissue phase (cf. 7) of the disease. It is also effective in the treatment of clinical attacks of malaria, being curative in falciparum but not in vivax malaria. The response of fever and symptoms in each infection is somewhat less prompt

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