Rats reared in an enriched condition (EC) display less sensitization to nicotine than rats reared in an impoverished condition (IC). However, it is unknown what effect differential rearing has on nicotine-induced conditioned hyperactivity. The present study determined whether differential rearing affects nicotine-induced conditioned hyperactivity. This study also examined the effects of mecamylamine on conditioned hyperactivity and sensitization. EC, IC, and social condition (SC) rats were reared from 21 to 51 days of age before receiving repeated nicotine injections (.4 mg/kg) prior to 1-h locomotor sessions. Following the conditioned-hyperactivity test, rats received additional training sessions followed by a drug-free rest period before the sensitization test. Mecamylamine (1.0 mg/kg) was administered prior to the conditioned-hyperactivity test and sensitization test. Nicotine treatment resulted in sensitization and conditioned hyperactivity in all differential rearing groups. EC rats displayed less locomotor activity in response to nicotine than both IC and SC rats. Pretreatment with mecamylamine blocked the expression of conditioned hyperactivity only in EC and SC rats and attenuated sensitization in all three rearing groups. These findings suggest that environmental enrichment may alter nicotinic acetylcholine receptors during development and may be a protective factor in the initiation and relapse of smoking behavior.