Depending on the implementation, a different set of 64 characters is used to represent the 64-digit values for the basis. The general strategy is to pick 64 characters that are common to most encodings and can be printed. This mix makes it rare that data could be tampered with when in transit through information networks that were not previously 8-bit clean, such as email.

For the first 62 values, MIME’s Base64 implementation uses A–Z, a–z, and 0–9. UTF-7 is an example of a variety that shares this property but differs in the symbols used for the last two values.

The first examples of this form of encoding were designed for dial-up connectivity between devices running the same operating system — for example, uuencode for UNIX, BinHex for the TRS-80 .

for example, uuencode for UNIX, BinHex for the TRS-80 (later modified for the Macintosh) — and thus could make further choices on which characters were safe to use. For example, uuencode only uses uppercase letters, digits, and a lot of punctuation, but no lowercase.