A series of 4,5-disubstituted-1,2,4-triazole-3-thione derivatives (4a-e) and their N-Mannich bases (5a-e), together with a S-benzyl derivative (6), were synthesized and evaluated as antimycobacterial and antiproliferative agents. The structures of the compounds were established by IR, H-1-NMR, C-13-NMR and D-2-NMR spectroscopic methods and microanalysis. 4 and 5 were screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27294). Three of the tested compounds (4d, 4e and 5e) were found to be active in the primary screen. Among them, compound 4e was the most potent one with IC90 and IC50 values of 27.5 and 20.8 mu g/ mL, respectively. Additionally, compounds 4b, 4c, 5b, 5c, 5e and 6 were subjected to the NCI's in vitro disease-oriented antitumor screening to be evaluated for antitumor activity at a single dose of 10 mu M. The S-benzyl derivative 6 exhibited promising antiproliferative activity against leukemia CCRF-CEM, RPMI-8226 and SR, non-small cell lung cancer HOP-92, melanoma UACC-62 and renal cancer UO-31 cell lines.