Inbred mouse strains showing variability in spontaneous exploratory behaviors displayed differential responsiveness to diazepam in an anxiety-related exploration model. C57B1/6J, BALB/cJ, Swiss Webster/NIH, Swiss Webster/Harlan Sprague-Dawley, and CF-1 mice demonstrated a significant correlation between baseline exploratory activity and maximal percentage increase in exploratory behavior induced by diazepam. No correlation was seen between those behavioral responses and the characteristics of brain benzodiazepine binding sites in the different strains. Anti-anxiety responsiveness appears to be a function of some genetically-determined substrate for spontaneous exploratory behaviors which may have multiple neurochemical substrates.