To describe the behavioral and physiological responses associated with colic, the responses of 20 two-month-old infants with and 20 without colic were studied during a physical examination. Parents kept a diary of infant behaviors (including crying and fussing) for 3 days following the visit. Using Wessel, Cobb, Jackson, Harris, & Detwiler criteria, colic was defined as fussing/crying for 3 hr or more on each of the 3 days. Behavioral data coded by "blind" observers showed that during the physical exam, colic infants cried twice as much, cried more intensely, and were more inconsolable than were control infants. Despite these behavioral differences, heart rate, vagal tone, and cortisol measures indicated no appreciable difference in physiological responsivity for the two groups. At home, parents collected saliva cortisol samples at wakeup, midmorning, midafternoon, and evening for 2 days. In a finding similar to that shown by the laboratory data, the colic and control infants did not have different levels of daily average cortisol. These laboratory and home data provide no evidence of greater responsivity in the physiological substrate of difficult temperament for colic infants and are consistent with evidence of similarity in temperament once colic is resolved. At home, compared with control infants, colic infants did display a blunted rhythm in cortisol production. By diary, they also slept about 2 hr less per day than did control infants. Nighttime sleep was still significantly different when fussing/crying was statistically controlled. These data suggest that colic might be associated with a disruption or delay in the establishment of the circadian rhythm in activity of the hypothalamic-pituitary-adrenocortical axis and associated sleep-wake activity.