Abstract In agreement with previous work, [ 60Co]γ-irradiation shortly after phytohemagglutinin (PHA) stimulation, induces higher frequencies of chromosomal aberrations in trisomy 21 lymphocytes compared to normal controls. However, equal frequencies of chromatid aberrations are induced in fully-stimulated trisomy 21 and normal lymphocytes by irradiation during G 2. We have observed that trisomic lymphocytes respond more rapidly to PHA stimulation than normal lymphocytes. Furthermore, we have observed that chromosomal radiosensitivity increases as a function of time after PHA stimulation in normal lymphocytes. When normal lymphocytes are irradiated 8 h after PHA stimulation, the frequencies of chromosomal aberrations induced are comparable to those induced in trisomy 21 lymphocytes irradiated 30 min after PHA stimulation.