Treatment of maternal phenylketonuria (PKU) consists of a low phenylalanine diet, begun before conception, which is believed to prevent mental retardation, microcephaly, and congenital heart disease in offspring of women with PKU. Experiences in treating these women indicate that their cooperation with medical recommendations is generally poor. We present a psychosocial model on adjustment and coping in maternal PKU. The proposed model defines four stages in the reproductive years of women with PKU, each of which has specific behavioral goals. The four stages are: (1) prevention of unplanned pregnancies; (2) reproductive decision-making; (3) diet initiation; and (4) diet continuation through pregnancy. Review of the literature on the different behaviors expected at the different stages enabled indentification of psychosocial factors that may explain success or failure in achieving the goals at each stage. Based on this theoretical framework, practical implications for treating women with PKU have been suggested.