To study the role of endogenous opioid peptides in the regulation of behavioural responses to novelty, male mice from the inbred strains SRH, SRL, C57BL/6, and DBA/2 were injected IP with either saline alone, or the opiate antagonist naloxone, dissolved in saline, in dosages of 4 or 8 mg/kg. After 10 min, the animals were placed individually for 20 min in a novel environment and some 12 behavioural components were recorded. Naloxone reduced grooming and incipient rearing in all four strains and it reduced sniffing, leaning against the wall, and locomotor activity in some of them. Object-sniffing, object-learning, defecation, freezing, and Straub tail elevation remained unaffected. The results for grooming and locomotor activity are largely in agreement with reports from others. Rather unexpectedly, the drug enhanced rearing responses in all strains. Although in several cases, a genotype-treatment interaction became apparent, the observed strain differences usually persisted and the correlations found between the behavioural components did not alter much. The naloxone-induced reductions in sniffing, leaning, locomotion, and grooming suggest endogenous opioid involvement in the control of behavioural activation in a novel situation. The increases in rearing possibly result from an additional agonist action of naloxone.