Three novel series of 5,7-diaryl-2-(pyridyl)-1,2,4-triazolo[1,5-a]pyrimidines were prepared as antibacterial and antifungal agents. The triazolopyrimidines (21-23)a-m were synthesized by reaction of the respective 3-amino-5-(2-,3- or 4-pyridyl)-1,2,4-triazoles (14-16) with substituted chalcones analogues (17a-m) in ethylene glycol. As the cyclocondensation reaction of such heterocyclic amines with α,β-unsaturated ketones might produce isomeric triazolopyrimidines, the isolated products were identified by studying their IR, 1H-NMR and MS. Their purity have been ascertained through TLC and elemental analyses. The antibacterial activity of the prepared compounds was screened against several bacterial species in comparison to Amoxycillin. As general features the 2-pyridyl series (21a-m) exhibited higher activity than the corresponding 3- or 4-pyridyl analogues (22-23)a-m. The 3-pyridyl derivatives (22a-m), particularly those having electron-donating substituent on the phenyl nucleus, showed selective antibacterial activity against S. marcescens. The synthesized derivatives were tested for antifungal activity, in comparison to Clotrimazole but no activity has been observed.