Infants between 1 and 6 months of age (mean age 3.6 months) who were referred to the Munich Interdisciplinary Research and Intervention Programme because of persistent crying and their mothers were examined and compared with an age-matched community-based control sample with no current cry problem. Three groups, referred extreme criers, referred moderate criers, and controls, were compared with regard to measures of psychosocial and organic risks, the mothers' perception of her own psychological state and infant temperament, the quality of mother-infant relationship, and intuitive parenting in mother-infant face-to-face interactions. In comparison with general-community samples of infants with persistent crying, the present clinical sample represents a biased group with particularly high levels of infant distress for long periods of time, with problems of sleep-wake organization, neuromotor immaturity, and difficult temperament. Moreover, extreme crying was associated with a cumulation of organic and psychosocial risks, including high rates of prenatal stress and anxiety, maternal psychopathology and partnership conflicts. Mothers in both referred groups scored similarly low on feelings of self-efficacy, and high on depression, anxiety, exhaustion, anger, adverse childhood memories, and marital distress. Mother-infant relationships were more often distressed or disturbed among referred dyads than among controls, and 40% as compared with 19% showed dysregulatory patterns of interactional failures in face-to-face contexts. The findings suggest that factors related to parental care did not cause persistent crying, but functioned as maintaining or exacerbating factors. Dynamic interactions between persistent crying, difficult temperament, and parenting factors which compromise maternal resources and intuitive parenting may put such families at long-term risk for both relationship and behaviour problems.