Several studies have reported radioprotective, antimutagenic, anti-inflammatory, antinociceptive, and anticancer effects of bee venom both in the cell and the whole organism. The aim of this study was to assess the effects of a single high dose of 100 μg mL-1 of whole bee venom in human lymphocytes in vitro over a variety of time spans (from 10 min to 24 h). After the treatment, we used the comet assay and micronucleus test to see the effect of bee venom on the cell. The comet assay confirmed that the venom damaged the DNA molecule. Tail length, tail intensity, tail moment showed a significant increase (P<0.05). The percentage of long-tailed nuclei (LTN) with the tail length exceeding the 95th percentile also increased in a time-dependent manner. The micronucleus parameters (number of micronuclei, nucleoplasmic bridges, and nuclear buds) also showed a significant time-dependent increase (P<0.05). This research indicates that high concentrations of bee venom can lead to cellular instability. Further research is needed to understand the mechanism of action of bee venom and its components in human cells and to see if this natural product may find application in medicine. Cilj ovog istraživanja je procjena staničnog statusa ljudskih limfocita periferne krvi nakon tretmana visokom koncentracijom pčelinjeg otrova u in vitro uvjetima primjenom alkalnog kometnog testa i mikronukleusnog testa. Limfociti su bili izloženi pčelinjem otrovu u koncentraciji od 100 μg mL-1 u različitom vremenu (od 10 min do 24 h). Rezultati kometnog testa upućuju na oštećenje molekule DNA povećanjem parametara kometnog testa (dužina repa, intenzitet repa i repni moment) te prisutnost limfocita s visokom učestalosti kometa s dugim repovima (LTN). U tim stanicama učestalost LTN premašuje 95% ukupne raspodjele vrijednosti LTN dobivene za sve stanice kontrolnog uzorka. Parametri mikronukleusnog testa (broj mikronukleusa, nukleoplazmatski mostovi i nuklearni pupovi) također pokazuju značajan porast u odnosu na odgovarajući kontrolni uzorak (P<0,05). Rezultati dobiveni ovim tehnikama upućuju na to da pčelinji otrov u visokoj koncentraciji uzrokuje staničnu nestabilnost te na potrebu daljnjih istraživanja mehanizama djelovanja pčelinjeg otrova i njegovih sastavnica na ljudske stanice u svrhu primjene prirodnih spojeva posebice u medicinskoj praksi.