Male rats were receiving nicotine (base), 50 mg/kg in their drinking fluid for 9 and 41 weeks, respectively. A markedly reduced intake of fluid was observed during both regimes of nicotine treatment. At withdrawal of nicotine after 9 weeks of treatment the intake of water was immediately increased up to control level while in rats with 41 weeks of exposure the intake of drinking fluid increased to 65% over the control level still 14 days after withdrawal of nicotine. Tolerance to nicotine was measured after 7 days of abstinence in rats treated for 9 weeks. No significant change in cholineacetyltransferase (ChAT) activity or number of muscarinic binding sites in brain was observed after 9 or 41 weeks of nicotine treatment. Twenty-four hours after withdrawal from the 41 weeks nicotine treatment there was a significant increase of 46% in the number of [3H] nicotine binding sites in the hippocampus while the number of binding sites was decreased by 44% in the cortex and unchanged in the midbrain. On day 14th of abstinence these changes had disappeared. Following 9 weeks of nicotine treatment no change in [3H] nicotine binding was observed after 24 h or 7 days of abstinence.