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An analysis of 80 British parent–offspring trios by Wei and Hemmings in 2000 revealed thre1e out of five markers within the NOTCH4 locus to be strongly associated with schizophrenia. In our present study, we have examined NOTCH4 markers in large samples of German and Palestinian-Arab origin.Our study population comprised a German case–control sample (n=512 schizophrenia patients and n=232 controls) and two independent parent–offspring trio samples of German (n=159 trios) and Palestinian-Arab (n=208 trios) descent. We examined a total of ten single nucleotide polymorphisms within the NOTCH4 locus and the adjacent loci, spanning a region of approximately 100 kb.Neither single marker nor haplotype analyses showed association with schizophrenia. In addition, analyses of the German case–control and trio samples revealed no significant association between NOTCH4 polymorphisms and early-onset schizophrenia.Our results suggest that NOTCH4 is unlikely to play a major role in the genetic predisposition to schizophrenia in the German or the Palestinian-Arab population.