Studies on filariasis were done on wild cotton rats harboring Lito-mosoides carinii. Compds. were given intraperit. at maximally tolerated doses every 8 hrs. for a total of 18 doses. 4.0 hrs. after the last injn., autopsy was performed, and the filariae removed aseptically; worms from untreated rats were observed for comparison. Unaffected worms usually remained motile for at least 2 days. One compd., (l-amyl-2,-5-dimethyl-3-pyrrole) (l,6-dimethyl-2-quinoline) dimethine-cyanine chloride (Chemotherapy Center #348) was completely curative; 0.1 mg./kg. per injn. regularly killed all worms in all treated animals. The cyanines were also strikingly active in vitro. The oxidative metabolism was inhibited by cones. of 1: 25,000,000 to 1:6,000,000; it is postulated that the drugs act by inhibiting one or more enzyme systems. Almost all cyanines show the effect to some extent. Any modification which destroys the possibility of amidinium-ion resonance in the compds. causes a disappearance of high activity. The effectiveness of intraperit. administration once daily was slightly greater than that following administration every 8 hrs. In cotton rats, cures were almost invariably produced when compound #863 was given intraven. in doses of 1 mg./ kg. 3 to 6 times at intervals of 1, 3, or even 7 days. Toxic effects were seen only with individual doses of 10 mg. or more per kg. There was a mild and reversible renal damage. There was also a transient hypotensive effect with compensatory tachycardia. A method for the extraction of #863 from tissues and its spectrophotometric detn. at 494 mu has been devised. The compd. #863 has been given intraven. to 27 human patients with no signs of toxicity other than mild transient hypotension and tachycardia.