The relationship between urinary excretion of sex-dependent low molecular weight proteins (LMWP) in male rats and narcotic dependence is described in this study. Rats were intermittently infused with narcotics at one hour intervals through an implanted intravenous cannula. Development of physical dependence on morphine, pethidine, and pentazocine was detected by withdrawal signs including body weight loss and abnormal behaviors after naloxone challenge. In these animals, a significant decrease in urinary LMWP excretion was found following the second day of each drug treatment without significant changes in albumin excretion, and this decrease was observed continuously throughout the experiment. The markedly decreased level of LMWP recovered to the control level within 7 d after withdrawal of the drugs. These results suggest that the decrease in urinary excretion of sex-dependent LMWP in male rats is a phenomenon closely related to narcotic dependence.