(HC3) is a derivative of diphenyl (Long & Schueler, 1954;Schueler, 1955), with high but somewhat variable toxicity. Death in small animals follows respiratory paralysis of delayed onset; this is usually explained as being the result of the inhibition of acetylcholine synthesis. There is evidence that HC3 can affect choline metabolism in other ways and has some actions which occur immediately after its administration (Gardiner, 1961;Domer & Gardiner, 1968). It is uncertain whether these other actions are involved in the lethal intoxication, so we are studying analogues of HC3 in which the balance between the various actions might be different. This communication reports some experiments with the p-terphenyl analogue (TPHC3) of HC3.The LD50 following intraperitoneal injection into mice was 95 ,ug/kg for HC3 and 80 ,ug/kg for TPHC3. These values were determined simultaneously with groups of mice from common stock; on other occasions the values varied between 150 and 50 ,tg/kg for either substance.Both HC3 (10-4M) and TPHC3 (10-4M) strongly inhibited the synthesis of acetylcholine by guinea-pig brain mince and with either the inhibition was less if choline (10-'M) was present.Inhibitory effects were produced by both substances on the responses of isolated tissues involving acetylcholine. The toad isolated rectus abdominis and the guineapig isolated ileum were immediately and reversibly depressed by concentrations greater than 106M; the spontaneous activity of rabbit jejunum was more resistant, being affected when the concentration of HC3 or TPHC3 was raised to 104M.Either substance (0.5 mg/kg intravenously) in chicks produced an immediate curare-like paralysis of the legs and wings which was antagonized by choline (80-100 mg/kg). In the rat the effects on neuromuscular transmission were studied by recording the contractions of both gastrocnemius muscles in response to the stimulation of the sciatic nerves. The nerves were regularly stimulated every 5-10 sec for 0.2