OBJECTIVE: Impact of caregiver characteristics, patient variables, and regional differences on family burden. METHOD: Two hundred and eighteen schizophrenia patients and key-relatives of an urban and a rural area were examined five times over 30 months. Patients’ psychopathology, service utilization; relatives’ burden, coping abilities and contact duration with the patients were recorded. Effects of interpersonal differences and intrapersonal changes over time were analyzed with regression models. RESULTS: Interpersonal differences (patients’ positive and negative symptoms, relatives’ coping abilities, and patient contact) and intrapersonal changes (relatives’ coping abilities, patients’ negative symptoms and utilization of community care) predicted family burden. CONCLUSION: Family education programs should help caregivers to improve their coping strategies. Therapy solutions must address negative symptoms just as much as positive symptoms, as these especially impact caregivers. Intensified community-based care can reduce burden, but provision alone is not sufficient. Psychiatrists and caregivers should motivate patients to take advantage of such offers.