The authors studied the association of Alzheimer's disease (AD) with total plasma homocysteine (tHcy) and apolipoprotein E (apoE) genotype, and the usefulness of measuring medial temporal lobe thickness (MTL) thickness for the diagnosis of AD in Sri Lankan patients. Using criteria of the NINCDS-ADRDA, 23 AD patients and 21 controls were recruited. All underwent MTL-oriented computed tomographic (CT) scans, measurement of plasma tHcy, and apoE genotyping. Mean plasma tHcy was significantly higher in AD patients than controls (p=.001). This association was independent of age, sex, body mass index (BMI), serum folate and vitamin B12, and serum creatinine. The frequency of apoE4 allele was significantly higher (p=.003) in AD patients, and the adjusted odds ratio of AD for the presence of one or more apoE4 alleles compared with none was 10.39 (95% CI 1.77-61.10; p=.010). The mean minimum MTL thickness was significantly higher in control subjects compared to that of AD patients (p<.001). This first report of apoE4, plasma tHcy, MTL thickness, and AD from Sri Lanka shows that high plasma tHcy, the presence of apoE4 allele, and MTL atrophy are associated with AD.