The N-3 amino derivatives m of daT, AZT, 3'-FddT, and D4T were prepared by electrophilic amination of the parent compounds. Although compounds z 2, and a were essentially inactive, N-3 amino AZT 8 (RP67042) maintained activity and displayed lower toxicity and a longer plasmatic haljlije compared to AZT.. A wide range of 2',3'-dideoxynucleoside analogs have been prepared.1 in the search for new, long acting, highly selective, and non toxic anti-HIV agents to replace AZT.2 As an outcome essentially four modifications of the sugar component, as in AZT 1. ddT 2, 3'-FddT 3, and D4T 4, result in potent anti-HIV activity.2.3,4,5 Alterations of the pyrimidine and purine base component have also been studied. However, the influence of substitution at the N-3 position of the thymine base on HIV replication has not been evaluated, which may not seem suprizing in view of the importance of this position in base pairing to adenosine in DNA.6 In this communication we report the preparation of the N-3 amino derivatives u of ddT, AZT, 3'-FddT, and D4T, and describe the anti-HIV activity determined for N-3 amino AZT 8 (RP67@42).7