The possible impact of menstrual phase upon reactivity to nicotine was investigated in 12 healthy women smokers. Controlled doses of nicotine were administered via an intranasal aerosol delivery device to overnight-deprived women smokers in four hormonally verified menstrual phases. Physiological, biochemical, and subjective measures were collected. Cycle-related symptomatology differed significantly across phase, with lowest values during the mid-follicular phase. No significant differences were found for baseline variables, including withdrawal measures. Nicotine increment was stable across phase, confirming reliability of the dosing method. No significant menstrual phase differences were found for physiological, subjective, or biochemical responses to nicotine. Pending investigations conducted over longer intervals, in a wider variety of subjects, findings suggest that for this type of study, complex strategies to control for menstrual-cycle phase effects may be unnecessary. (C) 1998 Elsevier Science Ltd.