The hypothesis that the dexamethasone suppression test (DST) and rapid-eye-movement (REM) latency test are not biological markers for depressive illness but artifacts arising from dietary and sleep disturbances that accompany depression was examined in 28 normal volunteers. The restriction of calorie intake with moderate weight loss reproduced a pattern of response to dexamethasone closely resembling that claimed to be diagnostic of depressive illness. The shortened REM latencies claimed as a diagnostic marker were replicated in volunteers by mimicking the sleep pattern commonly found in depression. These changes could not be explained by the induction of mood disorder in the subjects. The results put in question the diagnostic value of the DST and REM latency tests in clinical practice, where sleep disorder and poor appetite, with reduced calorie intake, are the common accompaniments of depressive illness.