The main characteristic that distinguishes prokaryotes and eukaryotes is the presence or absence of a true nucleus.

Prokaryotes lack a membrane-bound nucleus. Their DNA is located in a region called the nucleoid, which is not enclosed by a membrane. They also lack other membrane-bound organelles.

Eukaryotes, on the other hand, have a true nucleus, which contains their genetic material (DNA) enclosed within a membrane. They also possess other membrane-bound organelles, such as mitochondria, Golgi apparatus, endoplasmic reticulum, etc.

Here's a table summarizing the key differences:

| Feature | Prokaryotes | Eukaryotes |

|-----------------|-----------------------|--------------------------|

| Nucleus | Absent | Present |

| Organelles | Absent (except ribosomes)| Present |

| Cell Size | Typically smaller | Typically larger |

| DNA Structure | Circular | Linear |

| Examples | Bacteria, Archaea | Animals, plants, fungi |