Flow cytometric DNA and proliferative compartment (S + G2M) analysis was performed on lymph nodes from 37 patients with Hodgkin's disease (HD) and on 16 lymph nodes plus 6 extranodal biopsies from 22 patients with peripheral T-cell lymphomas (PTCLs). The mitotic rate per 20 high-power fields (HPFs) was also determined for each case. The PTCLs showed significantly higher proliferative activity than the HD cases, as evidenced by a mean S + G2M of 12.0% versus 5.0% for HD and a median mitotic rate of 27 versus 5 mitoses per 20 HPFs in the HD cases. Because morphologic distinction, particularly of mixed cellularity HD (HDMC), from the diffuse small cleaved cell (DSCCL) or mixed cell (DMCL) pattern of PTCL may at times be difficult, these subgroups were compared separately. The 2 cases of DSCCL plus 12 of DMCL yielded a higher proportion of S-phase cells than the 9 HDMC cases with S + G2M means of 9.9% versus 3.3% and a higher mitotic rate, median 21 versus 7 per 20 HPFs. These findings suggest that S-phase determination and mitotic rate provide additional parameters in discriminating PTCL from HD in the most histologically similar cases.