Mercury distribution, food consumption, body weight, andin vivoprotein synthesis were compared as criteria for evaluating the efficacy of D‐penicillamine (DPA) in treating experimental methyl mercury (MM) intoxication. Female rats were orally administered MM hydroxide at 40 mg/kg and, after a 7‐ to 8‐d latency period, displayed characteristic neurological signs of MM intoxication. Within 24 h of MM exposure food consumption decreased 75%, causing a 12‐g drop in body weight, and synthesis of whole blood and kidney protein increased. Protein synthesis in lifer was increased 39% by MM after 3 d, and that in cerebellum was decreased 15% after 7 d. Treatment with DPA (1.2 g/kg·d sc on d 2, 3, and 4) prevented the appearance of neurological signs. DPA lowered the Hg content of all tissues; restored food consumption to control levels; increased the onset and amount of body weight gain; returned synthesis of blood, liver, and kidney proteins to control levels; and prevented the decrease in protein synthesis in cerebellum. By itself, DPA produced a transitory decrease in both food consumption and body weight, which could be prevented with vitamin B6. Vitamin B6antagonized DPA's reversal of MM's action on protein synthesis. Furthermore, DPA and/or vitamin B6had a variety of effects on protein synthesis in control rats. Thus it was not possible to use protein synthesis to predict the efficacy of the combination of DPA and vitamin B6as found for the parameters of food consumption, body weight, and Hg distribution. Since changes in body weight and food consumption were the earliest and most pronounced and consistent responses to MM and effective DPA treatment, they were considered the best criteria for evaluating treatment efficacy in experimental MM poisoning in rats.