Epidemiological evidence suggests alcoholic myopathy is more severe in females than males, but comparable animal studies are lacking which makes elucidating the biochemical locus for this defect problematic. The present study determined whether skeletal muscle protein synthesis and markers of degradation exhibit a sexual dymorphic response to either chronic alcohol consumption or acute intoxication. Male and female rats were fed an alcohol-containing diet or pair-fed for 26 wks (chronic), or received an intraperitoneal injection of alcohol (acute). In males, chronic alcohol decreased gastrocnemius protein synthesis by 20%. This reduction was associated with a 2-fold increase in the inactive eIF4E-4EBP1 complex and a 60% reduction in the active eIF4E-eIF4G complex. This redistribution of eIF4E was associated with decreased phosphorylation of both 4E-BP1 and eIF4G (50-55%). The phosphorylation of ribosomal protein S6 was also reduced 60% in alcohol-fed male rats. In contrast, neither rates of protein synthesis nor indices of translation initiation in muscle were altered in alcohol-fed female rats, despite blood alcohol levels comparable to males. Chronic alcohol ingestion did not alter atrogin-1 or MuRF1 mRNA (biomarkers of muscle proteolysis) in males, but increased their expression in females 50-100%. Acute alcohol intoxication produced a comparable decrease in muscle protein synthesis and translation initiation in both male and female rats. Our data demonstrate a sexual dimophorism for muscle protein synthesis, translation initiation and proteolysis in response to chronic, but not acute, alcohol intoxication, however, they do not support evidence indicating females are more sensitive toward the development of alcoholic skeletal muscle myopathy.