This study focuses on cultural loaded vocabulary in Persian (L1) and its possible effect on acquisition and retention of new words in English (L2). The term cultural loadedness refers to cultural differences between L1 and L2 vocabulary (Qi-wen, 2010): a number of Persian words exhibit different communicative appropriateness or negative feelings compared to their English counterparts. For instance, wine is interpreted into the Persian 'sharaab', a religious drink that creates negative feelings. The research was conducted on 90 participants, who were asked to read texts and interpret 10 target words: 5 culturally loaded and 5 culturally neutral. The group of words involved four verbs, four nouns and two adjectives. Additionally, these words were tested in terms of frequency in English through the Collins COBUILD dictionary and the word frequency categorization system (Paribakht 2005). The results suggest that when speakers deal with culturally loaded words, their equivalents in Persian do not sufficiently describe their semantic features due to semantic mismatch. Since Persian learners of English cannot benefit from it, it is assumed that greater exposure in L2 is necessary along with explicit instruction so as to compensate for such differences.