The present study extended testing of our biobehavioral model describing the effects of arousal and caffeine to include an examination of gender differences and their interactions with habitual and acute caffeine ingestion. Males and females selected as high or low habitual caffeine users were randomly assigned to receive either caffeine or a placebo and exposed to novel and repetitive recall tasks and to simple auditory stimuli. Electrodermal activity and recall task performance were recorded. The four major factors examined, including habitual caffeine use, acute ingestion, gender, and stimulus novelty, affected behavior, physiology, or both. Results showed that habitual caffeine usage systematically affected tonic arousal (skin conductance level) and improved recall task performance. Acute caffeine ingestion increased phasic arousal (skin conductance response amplitude) and reduced habituation rates. Gender interacted with other factors to significantly affect both tonic and phasic arousal, and females performed better than males on the recall tasks. These results were partially supportive of the theoretical model, and further work is needed to examine the interactions of acute and chronic caffeine intake with gender and novelty.