Renal transplant recipients are at risk of developing various infectious and non-infectious complications affecting the central nervous system (CNS). There is paucity of data regarding the spectrum of CNS complications and the epidemiology of infective agents varies according to geographical location. We retrospectively studied the spectrum of CNS complications seen in 792 renal allograft recipients followed up at this tertiary care centre in north India over a 19-year period. Autopsy findings of 78 allograft recipients who died in the hospital were also reviewed and included. The brain was examined in 22 of these patients. Overall, 79 (10%) patients developed some form of CNS dysfunction with a mortality rate of 60.8%. CNS infections occurred in 31 renal allograft recipients (3.9% of total) and accounted for the largest group (39.2%). Fungi were the commonest etiological agents (21 patients) and were associated with a 70% mortality, with cryptococcal meningitis occurring in 12, mucormycosis in six, aspergillosis in one, and other unusual fungal infections in the remaining two patients. All patients with mucormycosis had a fatal outcome. The second largest group comprised of patients with non-uremic encephalopathies (23 patients, 29.1%) with metabolic encephalopathy occurring in 13, toxic encephalopathy in nine and hypertensive encephalopathy in one patient) and was associated with an overall mortality rate of 60.9%. Cerebrovascular accidents occurred in 12 patients (15.2%) and were associated with a mortality of 91.7%. Other CNS complications included treatment related complications in four (5.1%), primary CNS lymphomas in three (3.8%), and miscellaneous complications in six patients (7.6%). Patients with non-cryptococcal fungal infections of the CNS, hepatic and toxic encephalopathy and those with cerebrovascular accidents had the worst outcome. There was no relationship between the development of infection or stroke and the type of maintenance immunosuppression used. We conclude that complications involving the CNS occur in 10% of all renal transplant recipients and are associated a with high mortality, warranting early diagnosis and aggressive treatment.