We have recently found that, besides an increase in aggression, isolation increases social interaction in NIH Swiss mice. In the present study the effect of isolation in other behavioral paradigms and their relation to brain monoamine concentrations were investigated. Mice, isolated for 0-20 days, were tested in the holeboard test of exploration and locomotor activity, the plus-maze test of anxiety, and Porsolt's swim test of behavioral 'despair.' Isolation reduced exploratory head-dipping, increased locomotor activity and increased the preference of mice for the open arms of the plus-maze. The immobility time in the swim test was shortened in mice isolated for 2 or 5 days, suggesting an improved ability to cope with stressful situations. Monoamine assays failed to show significant changes in the noradrenaline, dopamine, HVA, 5-HT or 5-HIAA contents in the amygdala, hypothalamus, hippocampus or brain stem. The results indicate that isolation of NIH Swiss mice for less than three weeks induces several behavioral changes, but is not particularly stressful.