The effects of diazepam, I-propranolol and isamoltane (CGP 361 A) (I-isopropylamino-3[2-(I-pyrrolyl)-phenoxy]-2-propranol), a drug with beta-receptor blocking and anxiolytic-like properties, on behavioral responses in rats encountering either a novel object or a drinking bottle in an unfamiliar open-field ("neophobic" behavior) were evaluated. Diazepam (1-5 mg/kg p.o.) and isamoltane (0.5-1.0 mg/kg p.o.) showed a similar pattern of effects in both test paradigms used. They counteracted the fear-induced suppression of behavioral responses in the presence of novelty: they shortened the approach latencies, increased the exploration-oriented activities and reduced grooming. Propranolol, however, in comparison with isamoltane (1.0 and 2.5 mg/kg i.p.) at equivalent doses, failed to significantly change any of the parameters measured in either of the two test situations. The results therefore indicate that neophobic behavioral responses discriminate between central anxiolytic and peripheral beta-blocking actions of drugs and further validate neophobic behavior as an animal model of anxiety.