The effects of chlorpromazine hydrochloride (CPZ) on paraquat (PQ) poisoning were examined using male and female beagle dogs. Twenty-six dogs were divided into 3 groups of 21 PQ-poisoned dogs and a control group of 5 saline-treated dogs. Thirty minutes after the 21 dogs were given 20 mg PQ dichloride/kg body weight sc, groups of 7 dogs received 3 mg CPZ/kg im, 5 mg CPZ/kg im or 0.5 ml saline/kg im daily for 5 d. PQ-treated dogs exhibited dyspnea. Serum angiotensin I converting enzyme (AICE) activity of the PQ-treated dogs was elevated during days 1-3. Lung AICE activity of the PQ-treated dogs was slightly lower than the control group. Lung hydroxyproline content was not elevated in either dying or surviving dogs. Based on our biochemical evaluations, PQ-induced pulmonary fibrosis did not occur during the 24 d of this study. From days 2-12 post-PQ dosing, all the dogs in the PQ + CPZ (3 mg/kg) group died. Dogs in the PQ + CPZ (5 mg/kg) group and the PQ + saline group had 6/7 and 5/7, respectively, die from days 2-24. The survival rate of the PQ + CPZ-treated dogs was not prolonged when compared to the PQ + saline group. The expected CPZ-induced increased in survival times, concurrent reductions in mortality rates, and effects on serum and lung AICE activities were not observed.