Studies have established that grown children’s problems affect parental well-being, but a dearth of research has addressed daily interactions and biological systems that may underlie these associations. This study examined whether parents have different types of daily interactions with adult children who have problems and whether those interactions are associated with variations in parents’ diurnal cortisol rhythms. Middle-aged parents (n = 197) reported their interactions with adult children for seven consecutive days and provided saliva, analyzed for cortisol, three times a day (wake, 30 min after wake, bedtime) for four of those days. Parents were more likely to report negative encounters but not less likely to report positive interactions or contact with adult children who suffered from problems. Interactions with adult children who had physical–emotional problems had more immediate same day associations with cortisol whereas interactions with adult children who had lifestyle–behavioral problems had more delayed, or next day associations with cortisol. Daily interactions and their associations with the hypothalamic–pituitary–adrenal-axis may be important mechanisms by which adult children with problems negatively affect parental well-being.