Unexplained crying in infants aged 1 to 3 months is a common concern for Western parents and health services. This study examined the hypothesis that the crying is due to high infant responsivity, and provides evidence about the types of stimulation that trigger crying in infants who present with high responsivity. The sample included 93 eight-day-old infants from a community sample (47 females, 46 males; mean birthweight 3457g; mean gestation 39.4 weeks; mean Apgar scores 8.28 at 1 minute and 9.59 at 5 minutes). Infants were tested for their response to two standard, mildly challenging, procedures: a neurobehavioural test involving undressing, putting down, and handling, and the Guthrie test, involving a painful heel prick to obtain a blood sample. The infants' crying over 24 hours was recorded in parental diaries. Newborn infants who exhibited high responsivity during the neurobehavioural assessment cried, rather than fussed, the most at home. High responsivity during the neurobehavioural assessment also predicted those infants who cried a lot and met a definition of ‘colic’ at home. The findings support the responsivity hypothesis and show that infants with high responsivity are upset by undressing, putting down, and sustained handling. Explanations for this and implications for the management of infant crying and colic are discussed.