1. 1. Intraperitoneal administration of morphine sulphate twice daily in doses gradually increasing from 10 to 270 mg/kg/injection over a period of 6 days in rats induced dependence to morphine. 2. 2. Morphine dependence produced by this "rapid schedule" method significantly decreased body weight, mid-brain tryptophan and 5-hydroxytryptamine levels, but increased the activity of tryptophan hydroxylase and 5-hydroxyindoleacetic acid levels in mid-brain, hypothalamus and pons-medulla. 3. 3. Furthermore, the levels of dopamine in striatum and hypothalamus and those of norepinephrine in hypothalamus were significantly reduced. 4. 4. Withdrawal for 24 hr from morphine treatment failed to alter tyrosine hydroxylase and tryptophan hydroxylase activity. 5. 5. The 5-hydroxyindoleacetic acid level of mid-brain remained elevated well above the control values. On the other hand, concentrations of 5-hydroxytryptamine in mid-brain, norepinephrine in hypothalamus and mid-brain and of dopamine in hypothalamus remained depleted following morphine withdrawal. 6. 6. In striatum, dopamine level increased by 12% of morphine-dependent rats; however, the change was statistically non-significant. 7. 7. Our study suggests that in morphine-dependent rats, the synthesis and presumably the utilization of brain norepinephrine, dopamine and 5-hydroxytryptamine are enhanced. 8. 8. Data lends support to the possibility that alterations in the metabolism of these central amines are, at least in part, involved in the development of dependence to morphine and in the expression of characteristic abstinence signs exhibited during morphine withdrawal.