This study examines differences between subjects with zero, one or two or more new diseases in a period of three years, with regard to demographic characteristics, socioeconomic status, life style, medical family history and current diseases in the family, psychological and sociological characteristics. This was studied using a primary care based nested case-control study. Data were available from 3745 cases and controls, all aged 20 years and older. All subjects were sampled from the Registration Network Family Practices, which is a computerised continuous primary care database. Cases were defined as subjects with new multimorbidity (two or more new diseases) registered in a period of three years and two groups of controls were operationalised as subjects with either one or no new diseases registered in the same period. Determinants were assessed by means of a postal questionnaire. Increasing age, higher number of previous diseases and low socioeconomic status were strongly associated with both morbidity and multimorbidity. After adjustment for these basic variables, the occurrence of multimorbidity was more frequent among subjects who did not report (volunteer) work or study, who had an active coping style, a high occupational class and an external locus of control. Profiles for subjects at risk for morbidity and multimorbidity seem to differ.