The purpose of this investigation is to assess family stress, coping, perceptions of their infant, and alterations in mood that may result from the hospitalization of their critically ill newborn infant. Eligible patients were those infants hospitalized in the Special Care Nursery (SCN) at Christiana Care Health Services, who were born up to 31 weeks' gestational age. Twenty-seven families (mothers and/or fathers) completed four questionnaires at 2-week intervals during the course of their premature infants' hospitalization. Data were primarily evaluated by using analysis of variance (ANOVA)/multivariate analysis of variance (MANOVA). A score for neonatal acute physiology (SNAP) was obtained in each infant to assess the effect of the severity of neonatal illness on the questionnaire variables. Families with high stress scores on the Parental Stressor Scale had different coping strategies than those with less stress scores. A high level of maternal depressive symptomatology was associated with altered methods of coping, general stress, and perception of infant health. There was no relationship between the SNAP score on the overall level of stress families. Families who completed more than two questionnaires differed from those who only completed two or less questionnaires, although the sample size was too small to assess longitudinal changes in this study population. Level of stress and depressive symptoms are two major influences of how families cope with the current hospitalization of a premature infant. The degree of neonatal illness is not a major contributor to the parents' coping ability. Healthcare providers need to understand these dynamics when supporting families during the hospitalization of their premature infant.