Somatotropin exerts a powerful galactopoietic effect when it is administered to dairy cattle. The mechanism by which somatotropin increases milk yield is currently unknown. This study describes the relationship between long-term exogenous somatotropin injections, milk plasmin concentrations, and milk yield. Plasmin is a serine-protease involved in rodent mammary gland involution. Thirty-five control cows were shown to increase milk plasmin concentrations and decrease milk yield as their lactation period advanced past the 2nd mo. In 42 somatotropin injected cows, milk plasmin was maintained at low concentrations, and milking performance was enhanced. Cessation of somatotropin injections at drying off led to a rapid elevation of milk plasmin to control values. Our hypothesis is that somatotropin suppresses plasmin production within the mammary gland, thereby suppressing involution and allowing a persistence of milk production. During a normal lactation, gradually increasing amounts of plasmin within the mammary gland results in the gradual involution process.