Given the common pathways for uptake and synthesis for dopamine and serotonin, enhanced renal dopamine synthesis in response to increased substrate 3,4-dihydroxyphenylalanine (L-DOPA) is postulated to decrease renal serotonin synthesis. The present study compared the effects of chronic oral administration of L-DOPA on dopamine and serotonin excretion in vivo, with the effects of enhanced dopamine synthesis per nephron due to adaptation to reduced renal mass (RRM). Four groups of rats were studied: sham-operated rats and rats with RRM in the absence and presence of chronic oral L-DOPA. L-DOPA (2 mg · 100 g body wt¹ · day¹) for 6-14 days increased calculated dopamine synthesis per nephron in sham-operated rats from 2.0 ± 0.3 (n = 7) to 13.6 ± 1.8 pg · day¹ · nephron¹ (n = 7, P < 0.05) and in rats with RRM from 6.1 ± 1.3 (n = 7) to 39.3 ± 5.2 pg · day¹ · nephron¹ (n = 7, P < 0.05). Chronic oral L-DOPA concomitantly decreased serotonin synthesis per nephron in sham-operated rats (1.6 ± 0.1 to 1.0 ± 0.1 pg · day¹ · nephron¹, n = 7, P < 0.05) and in rats with RRM (5.6 ± 0.9 to 2.6 ± 0.4 pg · day¹ · nephron¹, n = 7, P < 0.05). Both serotonin and dopamine synthesis per nephron were increased in rats with RRM. In conclusion, chronic oral administration of L-DOPA enhances dopamine excretion and decreases serotonin excretion in normal rats and in rats with reduced renal mass. Both dopamine and serotonin excretions per nephron were elevated by renal mass reduction.