Background  In some of our patients with intellectual disabilities (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment. In these patients melatonin levels at noon were extremely high (>50 pg/ml). We hypothesise that the disappearing effectiveness is associated with slow metabolisation of melatonin because of a single nucleotide polymorphism (SNP) of CYP1A2.Method  In this pilot study we analysed DNA extracted from saliva samples of 15 consecutive patients with disappearing effectiveness of melatonin. Saliva was collected at noon and 4 pm for measuring melatonin levels.Results  In all patients' salivary melatonin levels at noon were >50 or melatonin half time was >5 h. A SNP was found in eight of 15 patients. The allele *1C was found in two patients and in six patients the *1F allele was found.Conclusions  Of 15 patients with disappearing effectiveness of melatonin, seven were diagnosed with autism spectrum disorder, and in four of them a SNP was found. The other eight patients were known with a genetic syndrome. In six of them behaviour was considered to be autistic‐type and in three of them a SNP was found. This finding may give a new direction for research into the genetic background of autism.