To investigate the relationship between three HTR4 gene polymorphisms, 83097 C>T, 83198 A>G as well as -36C>T polymorphisms, and attention deficit hyperactivity disorder (ADHD) comorbid or not comorbid disruptive behavioral disorder (DBD).Blood samples were taken from 152 trios with probands of ADHD comorbid DBD and 173 trios with probands of ADHD not comorbid DBD. DNA was extracted. 83097 C>T, 83198 A>G and -36C>T were genotyped by restriction fragment length polymorphism analysis. Transmit/disequilibrium test and haplotype analysis were used to test the association of the three polymorphisms with ADHD comorbid or not comorbid DBD separately.Haplotype T/G/T showed tendency of over transmission (chi(2)=3.470,P=0.062) to probands of ADHD with DBD, while haplotype C/G/T (chi(2)=4.568,P=0.032) and C/G/C (chi(2)=5.333,P=0.021) were under transmitted to probands of ADHD without DBD, No biased transmissions of any allele were found in families with probands of ADHD with and without DBD.Whether ADHD comorbid DBD or not comorbid DBD makes difference at the level of HTR4 gene polymorphisms.